Our objective is to study the pathophysiological basis of congenital murine hydrocephalus in the hy-3 and ch strains as models, so as to understand congenital human hydrocephalus. We are investigating the etiology of hydrocephalus in both of these mutants. Specifically we are studying the 1) cranium, 2) meninges and subarachnoid space, 3) brain parenchyma, 4) ventricular system, 5) ependymal cells, 6) choroid plexus in fetal, newborn, and adult normal and hydrocephalic mice, 7) changes in aqueduct, and 8) the central canal of spinal cord. Particular attention is being given to studying the relative changes in size, form, and position of the III and IV ventricles. The foramina of Luschka and Magendie as well as the aqueduct of Sylvius are being studied this year so as to evaluate ependymal changes as they relate to occlusion of the aqueduct and transitional ependymalarachnoid changes as they relate to functional patency of the outlet foramina of the IV ventricle. In addition to light and electron microscopic techniques for the study of these tissues, we are utilizing 1) ultrastructurally visible tracers, to investigate CSF dynamics; 2) histochemical methods, to characterize substances in the extracellular space of cerebral tissue and in the matrix of cartilaginous bone; 3) biochemical procedures, to analyze the acidic glycosaminoglycan content in normal and hydrocephalic mice; 4) microangiotomography of vascular changes in hydrocephalic mice; 5) perfusion models of the cisterns. In the ch strain, our hydrocephalic and normal litter-mate mice are obtained by Caesarean section, since affected animals of this strain die at birth. We have introduced in the hy-3 strain a dominant marker (Os) gene which is recognizable in mid-fetal life; this facilitates identification of hy-3 homozygotes in utero and in the early postnatal period, before this type of hydrocephalus begins to develop. We are correlating our finding of abnormalities - anatomic, histologic, biochemical, and functional with our clinical studies on hydrocephalic children. Bibliographic references: McLone, D.G., Bondareff, W. Developmental morphology of the subarachnoid space and contiguous structures in the mouse. Am. J. of Anatomy Vol. 142: 273-293, 1975.